Recent studies in our laboratory suggest that antibodies to GMI ganglioside are present in over 50 percent of patients with rigorously defined amyotrophic lateral sclerosis. The long-term objective of this protocol is to define the relationship between antiganglioside antibodies and human disorders of the motor neuron. Specifically, we plan: 1) to study the frequency, titers and types of anti-GMI ganglioside antibodies in patients with motor neuron diseases, 2) determine whether antibodies against other gangliosides are present in human motor neuron disorders, and 3) to study the possible pathogenetic effects of these human antiganglioside antibodies. Studies will be carried out using serums from humans with motor neuron disorders and controls. Methodology will include ELISA for quantitation of antibodies and thin-layer chromatography for characterization of antibody targets. Serum effects on motor axons will be evaluated after passive transfer to rats using light and electron microscopic methods. These studies relate directly to amyotrophic lateral sclerosis and clinically similar disorders of motor neurons. They should characterize possible pathogenic serum factors and suggest further therapeutic approaches in some patients with selective disorders of the motor system.